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Various Coupling Agents in the Phosphoramidite Method for Oligonucleotide Synthesis

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Synthesis of Therapeutic Oligonucleotides

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Abstract

This review selects some representative coupling agents used for internucleotide bond formation reactions in the phosphoramidite method, which is now the most widely employed method for the chemical synthesis of oligodeoxyribonucleotides and oligoribonucleotides, and it describes their utility, efficiency, and drawbacks. Moreover, the mechanism of the coupling of the nucleoside phosphoramidite and nucleoside promoted by the coupling agent is discussed in some cases. The selected coupling agents are 1H-tetrazole, 5-ethylthio-1H-tetrazole (ETT), 5-benzylthio-1H-tetrazole (BTT), 5-[3,5-bis(trifluoromethyl)phenyl]-1H-tetrazole (Activator 42), 4,5-dicyanoimidazole (DCI), certain carboxylic acids, and various acid/azole complexes such as benzimidazolium triflate (BIT) and saccharin 1-methylimidazole (SMI).

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Authors and Affiliations

  1. Graduate School of Information Science, Nagoya University, Nagoya, Japan

    Masaki Tsukamoto

  2. Department of Applied Chemistry, Faculty of Engineering, Aichi Institute of Technology, Toyota, Japan

    Yoshihiro Hayakawa

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  1. Masaki Tsukamoto
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  2. Yoshihiro Hayakawa
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Correspondence to Masaki Tsukamoto or Yoshihiro Hayakawa .

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Editors and Affiliations

  1. Osaka University, Suita, Osaka, Japan

    Satoshi Obika

  2. Tokyo Institute of Technology, Yokohama, Kanagawa, Japan

    Mitsuo Sekine

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Tsukamoto, M., Hayakawa, Y. (2018). Various Coupling Agents in the Phosphoramidite Method for Oligonucleotide Synthesis. In: Obika, S., Sekine, M. (eds) Synthesis of Therapeutic Oligonucleotides. Springer, Singapore. https://doi.org/10.1007/978-981-13-1912-9_2

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